The current proposal requests continuing support for a multidisciplinary General Clinical Research Center (GCRC) to serve as a physical and intellectual focus to encourage and support clinical research at the University of Pittsburgh Medical Center (UPMC). The objectives of the GCRC at UPMC are to provide an essential resource to elucidate mechanisms involved in the pathophysiology of disease states, develop and evaluate novel therapeutic strategies, teach potential clinical investigators, and integrate basic science with clinical medicine. An essential ingredient of this objective is to be able to undertake clinical research on clinically ill patients as well as normal subjects and relatively fit patients. To further these objectives, cooperative funding has been obtained from the NIH and UPMC to move from an 8 bed temporary facility with no outpatient provision to a purpose-built, 15 bed GCRC in the midst of an acute patient care area, together with a dedicated outpatient facility. In addition, scatter beds are proposed to permit clinical research in patients requiring aspects of clinical care not available on the GCRC. With the expanded resources available to clinical investigators, a number of themes of excellence in which several investigators are interacting are being fostered. These include: gene transfer for which the UPMC has provided and equipped a human gene therapy applications laboratory (HGTAL) to enable multiple investigator application of gene therapy; immune modulation, which involves both gene therapy and specific immune globulin therapy of different malignancies; endocrine regulation in a variety of areas, including diabetes, posterior pituitary function and fertility; behavioral research where the strength and depth of investigators at Western Psychiatric Institute and Clinic probe suicide, schizophrenia and affective disorders; and drug metabolism with an interdisciplinary focus ranging from epidemiology to new drug development. The GCRC proposal is to provide support to its investigators through an intensive GCRC biometry cohort of statisticians and a Clinical Data Management and Analysis System (CDMAS). In addition, comprehensive array of institutional laboratory facilities are made available to investigators through a GCRC/UPMC networking system. These include facilities requiring substantial equipment costs such as PET scanning and electron microscopy, or specific expertise such as is required in molecular biology, including peptide synthesis, protein sequencing, DNA synthesis, DNA sequencing, hybridoma formation of antibodies, cytogenetics, and flow cytometry, or in drug level measurements. Collectively, these proposed research projects provide a substantial resource to support clinical investigation and facilitate educating the next generation of clinical investigators.